南方医科大学学报杂志最新文献

Objective: To propose a dual-domain CBCT reconstruction framework (DualSFR-Net) based on generative projection interpolation to reduce artifacts in sparse-view cone beam computed tomography (CBCT) reconstruction.

Methods: The proposed method DualSFR-Net consists of a generative projection interpolation module, a domain transformation module, and an image restoration module. The generative projection interpolation module includes a sparse projection interpolation network (SPINet) based on a generative adversarial network and a full-view projection restoration network (FPRNet). SPINet performs projection interpolation to synthesize full-view projection data from the sparse-view projection data, while FPRNet further restores the synthesized full-view projection data. The domain transformation module introduces the FDK reconstruction and forward projection operators to complete the forward and gradient backpropagation processes. The image restoration module includes an image restoration network FIRNet that fine-tunes the domain-transformed images to eliminate residual artifacts and noise.

Results: Validation experiments conducted on a dental CT dataset demonstrated that DualSFR-Net was capable to reconstruct high-quality CBCT images under sparse-view sampling protocols. Quantitatively, compared to the current best methods, the DualSFR-Net method improved the PSNR by 0.6615 and 0.7658 and increased the SSIM by 0.0053 and 0.0134 under 2-fold and 4-fold sparse protocols, respectively.

Conclusion: The proposed generative projection interpolation-based dual-domain CBCT sparse-view reconstruction method can effectively reduce stripe artifacts to improve image quality and enables efficient joint training for dual-domain imaging networks in sparse-view CBCT reconstruction.

Objective: To investigate whether activation of mitochondrial acetal dehydrogenase 2 (ALDH2) alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.

Methods: Thirty 8-week-old C57 BL/6 mice were randomized into control, hypoxia, and hypoxia +Alda-1 (an ALDH2 activator) group (n=10), and the mice in the latter two groups, along with 10 ALDH2 knockout (ALDH2^-/-) mice, were exposed to hypoxia (10% O₂, 90% N₂) with or without daily intraperitoneal injection of Alda-1 for 4 weeks. The changes in right ventricular function and pressure (RVSP) of the mice were evaluated by echocardiography and right ventricular catheter test, and pulmonary artery pressure was estimated based on RVSP. Pulmonary vascular remodeling, right ventricular injury, myocardial α -SMA expression, distal pulmonary arteriole muscle normalization, right ventricular cross-sectional area, myocardial cell hypertrophy, and right cardiac hypertrophy index were assessed with HE staining, immunofluorescence staining and WGA staining, and the expressions of ALDH2, SIRT1, PGC-1α, P16INK4A and P21^CIP1 were detected. In pulmonary artery smooth muscle cells with hypoxic exposure, the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.

Results: The wild-type mice with hypoxic exposure showed significantly increased RVSP, right ventricular free wall thickness and myocardial expressions of P16^INK4A and P21^CIP1, which were effectively lowered by treatment with Alda-1 but further increased in ALDH2^-/- mice. In cultured pulmonary artery smooth muscle cells, hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16^INK4A and P21^CIP1, which were all lowered by treatment with Alda-1, but its effect was obviously attenuated by EX527 treatment.

Conclusion: ALDH2 alleviates hypoxiainduced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective: To investigate the effects of Shenqi Tiaoshen Formula (SQTSF) for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease (COPD) and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.

Methods: Forty-eight SD rats were randomly divided into control group, model group, low-, medium-, and high-dose SQTSF groups, and aminophylline (APL) group. In all but the control group, rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline, SQTSF or APL via daily gavage as indicated (starting from day 30). The rats were observed for changes in body weight, grip strength, lung function, lung pathology, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), oxidative stress levels, iron ion metabolism, cellular and mitochondrial ultrastructural changes in the lung tissue, and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.

Results: The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight, grip strength, and lung function parameters. Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial, perivascular, and alveolar inflammation and alveolar destruction, significantly increased IL-1β, TNF-α, IL-6, and IL-13 levels in BALF, and elevated pulmonary oxidative stress levels and Fe²⁺ and total iron ion concentrations. The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2, GPX4, and SLC7A11 and increased ACSL4 expressions in the lung tissue. Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.

Conclusion: SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective: To explore the mechanism by which Yigong San (YGS) improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation.

Methods: Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group, model group, donepezil (1.67 mg/kg) group, and YGS (7.5 g/kg) group and received the corresponding treatments via gavage once daily for one month. After the treatments, the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE, immunohistochemical and thioflavin S staining; ELISA and Evans blue method were used for detecting Aβ_1-40 and Aβ_1-42 levels in the brain tissue and serum and assessing blood-brain barrier (BBB) integrity. Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes. Western blotting was performed to detect the expressions of VE-cadherin, ZO-1, occludin, β-amyloid precursor protein (APP), BACE1, insulin-degrading enzyme (IDE), LRP1, RAGE, and AQP4 proteins.

Results: Compared with the control mice, APP/PS1 mice showed significant impairment of learning and memory abilities, increased degeneration or necrosis of hippocampal and cortical neurons, pathological scores, Aβ-positive plaques, elevated Aβ_1-40 and Aβ_1-42 levels in the brain tissue and serum, increased BBB permeability, upregulated RAGE expression, lowered expressions of VE-cadherin, LRP1, ZO-1, occludin, and AQP4 proteins, and reduced AQP4- expressing GFAP-positive cells. YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test, reduced hippocampal and cortical pathologies and Aβ-positive plaques, and ameliorated the abnormal changes in Aβ_1-40 and Aβ_1-42 levels, BBB permeability, protein expressions of RAGE, VE-cadherin, LRP1, ZO-1, occludin and AQP4, and the number of AQP4-expressing GFAP-positive cells.

Conclusion: YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

Objective: To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer (NSCLC) cells.

Methods: CCK-8 assay, colony formation assay, and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation, survival, and apoptosis of PC-9 and HCC827 cells, and their synergistic effect was evaluated using the SynergyFinder model. In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib, the changes in cell invasion and migration abilities were assessed with Transwell assay, and the expressions of apoptosis- and invasion/migration-related proteins (Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9) and the key PI3K-Akt pathway proteins were detected using Western blotting.

Results: In PC-9 cells, the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L, respectively, with a synergy score (ZIP) of 19.112; in HCC827 cells, their IC50 was 2.961 μmol/L and 7.934 μmol/L, respectively, with a ZIP of 12.325. Compared with aumolertinib and anlotinib used alone, their combined treatment more strongly inhibited the proliferation and survival, enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells. Western blotting showed that in both PC-9 and HCC827 cells, the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins, downregulated the expressions of Bcl-2, vimentin, MMP2, and MMP9 proteins, and reduced phosphorylation levels of PI3K and Akt.

Conclusion: Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway, suggesting a potentially new option for NSCLC treatment.

Objective: To investigate the impact of overwork on vascular endothelial barrier function in mice.

Methods: Thirty KM mice were randomized equally into control, overwork for 2 weeks (W2) group and 4 weeks (W4) group. In the latter two groups, the mice were subjected to continuous standing in water for 8 h followed by restraint for 3 h to simulate overwork on a daily basis for 2 and 4 weeks. After modeling, 4 mice from each group were intraperitoneally injected with Evans blue dye to assess vascular permeability. In the other 6 mice, serum IL-1β levels were measured using ELISA, and arterial tissues were collected for histological examination and detection of mRNA expressions of occludin, claudin-5, ZO-1, JAM-A and VE-cadherin; immunofluorescence assay was used to detect the protein expressions of claudin-5, ZO-1, VE-cadherin, and Syndecan-1.

Results: The mice in W2 and W4 groups exhibited slower weight gain, hair loss, reduced activity, and significantly increased serum IL-1β levels. Vascular permeability was significantly increased in W4 group. In W2 group, the endothelial cells were swollen and dissociated, and the intima was rough and irregular; arterial intimal rupture was observed in W4 group. The mRNA expressions of occludin, claudin-5, ZO-1 and JAM-A in the arterial tissues were significantly increased in W2 group but decreased in W4 group, while VE-cadherin mRNA expression were reduced in both groups (P < 0.05). The protein expressions of claudin-5, ZO-1, VE-cadherin, and Syndecan-1 were all significantly reduced in W4 group.

Conclusion: Prolonged overwork can cause damage of the intercellular junction complexes in arterial endothelial cells and the endothelial glycocalyx to result in impaired barrier function and increased vascular permeability in mice.

Objective: To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.

Methods: Male C57BL/6 mice were randomly divided into Sham group, cecal ligation puncture (CLP)-induced sepsis group, CLP with curcumin treatment (50, 100, and 200 mg/kg) groups, and CLP with both curcumin (200 mg/kg) and TRX-1 inhibitor PX-12 (25 mg/kg) treatment group. Inflammatory factors, MDA, MPO, and GSH levels in the lung tissue of the mice were detected. Beas-2B cells stimulated with lipopolysaccharide (LPS; 1 μg/mL) were treated with 2.5, 5, or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12, and the changes in MDA, Fe²⁺ and ROS levels were assessed. Western blotting was performed to detect the protein expressions of TXNIP, TRX-1, GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.

Results: The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6, IL-1β, TNF-α, MDA and MPO and decreased GSH expression. In Beas-2B cells, LPS stimulation significantly increased MDA and Fe²⁺ levels and ROS release, increased TXNIP protein expression, and lowered the protein expression levels of TRX-1, GPX4 and X-CT, and these changes were also observed in the septic mice. Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells. Curcumin significantly decreased the release of inflammatory factors, MDA and MPO, increased GSH level, lowered Fe²⁺, MDA and ROS levels, increased TXNIP protein expression, and lowered the protein expressions of TRX-1, GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells. The protective effect of curcumin was effectively blocked by PX-12 treatment.

Conclusion: Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Objective: To evaluate the effect of propofol, sevoflurane, and dexmedetomidine on respiratory complications in children undergoing fiberoptic bronchoscopy (FOB).

Methods: This double-blind randomized clinical trial was conducted among 120 children aged 1 month to 3 years undergoing FOB. The patients were randomized into 3 groups (n=40) for anesthesia induction with sevoflurane inhalation, 1 mg/kg propofol, or 1 μg/kg dexmedetomidine before bronchoscopy, and the changes in hemodynamic parameters, sedation level, and respiratory complications during and after the procedure were assessed.

Results: The patients' heart rate during bronchoscopy was significantly lower and the mean arterial blood pressure significantly higher in dexmedetomidine group than in sevoflurane and propofol groups (P < 0.05). Cough during bronchoscopy did not occur in any of the cases in propofol group, while the highest frequency of cough was recorded in dexmedetomidine group. The incidence of laryngospasm in the propofol group (12.5%) was significantly lower than those in sevoflurane and dexmedetomidine groups (30% and 32.5%, respectively) (P < 0.05).

Conclusion: Sevoflurane and propofol are safe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve better sedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

Objective: To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids (PHSTF) for rheumatoid arthritis (RA).

Methods: Twenty-five male SD rats were randomly divided into normal control group, RA model group, PHSTF treatment (45 and 90 mg/kg) groups, and Tripterygium glycosides (TPG) tablet (10 mg/kg) group (n=5). Except for those in the normal control group, all the rats were subjected to collagen-induced arthritis (CIA) modeling using a secondary immunization method, after which PHSTF and TPG were administered via gavage once daily for 4 weeks. After the treatments, serum levels of TNF-α and IL-1β were measured using ELISA, and ankle joint pathologies were assessed with HE staining; the expression of citrullinated histone H3 (Cit-H3), a neutrophil extracellular trap (NET) marker, in the ankle joints was evaluated with immunohistochemistry. In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester (PMA), the effects of PHSTF (100 and 200 μg/mL) on the expressions of Cit-H3, peptidylarginine deiminase 4 (PADI4), neutrophil elastase (NE), and myeloperoxidase (MPO) were examined with Western blotting; immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.

Results: In the CIA rat models, PHSTF significantly alleviated ankle swelling, decreased serum levels of TNF-α and IL-1β, improved histopathological changes in the ankle joints, and reduced Cit-H3 expression in both the serum and ankle joint cartilage. In the isolated rat neutrophils, PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.

Conclusion: PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective: To construct a model with a spatial and channel reconstruction convolutional module for accurate identification and classification of lung sound data.

Methods: We propose a convolutional network architecture combining the spatial-channel reconstruction convolution (SCConv) module. A lung sound feature extraction method combining the dual tunable Q-factor wavelet transform (DTQWT) with the triple Wigner-Ville transform (WVT) was used to improve the model's ability to capture the key features of the lung sounds by adaptively focusing on the important channel and spatial features. The performance of the model for classification of normal, crackles, wheezes, and crackles with wheezes was tested using the ICBHI2017 dataset.

Results and conclusion: The accuracy, sensitivity, specificity and F1 score of the proposed method reached 85.68%, 93.55%, 86.79% and 90.51%, respectively, demonstrating its good performance in classification tasks in the ICBHI2017 lung sound database, especially for distinguishing normal from abnormal lung sounds.